| Expression of nonmuscle cofilin-1 and steroid responsiveness in severe asthma. | |
| | |
MedLine Citation:
|
PMID: 17088134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Glucocorticoids are the mainstay of asthma therapy; however, a proportion of patients with asthma has a severe form of the disease that fails to respond to therapy. Understanding the molecular mechanisms behind glucocorticoid-insensitive asthma is therefore of clinical importance. Evidence in glucocorticoid-unresponsive Henrietta Lack (HeLa) cells indicated that cofilin-1 could act as an inhibitor of glucocorticoid function. OBJECTIVE: To determine whether cofilin-1 expression is abnormally expressed in cells from patients with severe glucocorticoid-insensitive asthma and examine the effect of cofilin-1 overexpression on glucocorticoid function. METHODS: Peripheral blood CD4(+) T cells were purified from 16 subjects with severe glucocorticoid-insensitive asthma and 16 subjects with mild glucocorticoid-sensitive asthma, and cofilin-1 expression was determined by quantitative real-time RT-PCR and Western blotting. The effect of dexamethasone on cofilin-1 expression was determined in Jurkat T cells, and the effect of cofilin-1 overexpression on anti-CD3/CD28-stimulated IL-2 release was measured. RESULTS: Peripheral blood CD4(+) T cells from subjects with severe glucocorticoid-insensitive asthma are less responsive to dexamethasone than cells from subjects with mild glucocorticoid-sensitive asthma. Cells from these patients express significantly (P < .05) higher levels of cofilin-1 than cells from subjects with mild asthma. Dexamethasone did not affect cofilin-1 expression in Jurkat T cells. Functionally, dexamethasone suppression of anti-CD3/CD28-stimulated IL-2 was attenuated in Jurkat cells overexpressing cofilin-1. CONCLUSION: These results suggest that increased cofilin-1 expression may be important in the regulation of glucocorticoid sensitivity in peripheral blood lymphocytes of patients with severe treatment-insensitive asthma. CLINICAL IMPLICATIONS: Understanding the mechanisms of enhanced cofilin-1 expression may lead to the development of new therapies for severe treatment-insensitive asthma. |
| | |
Authors:
|
Nisha Vasavda; Thomas Eichholtz; Atsushi Takahashi; Karen Affleck; John G Matthews; Peter J Barnes; Ian M Adcock |
Related Documents
:
|
10564464 - Towards deciphering the helicobacter pylori cytotoxin. 17549374 - Vegf-c, vegfr-3, and cox-2 enhances growth and metastasis of human cervical carcinoma c... 8262634 - Binding of the glycan of the major outer membrane protein of chlamydia trachomatis to h... 6398564 - Saturable attachment sites for type 3 mammalian reovirus on murine l cells and human he... 14983004 - Design of artificial cell-cell communication using gene and metabolic networks. 20354524 - Oncogenic kras sensitises colorectal tumour cells to chemotherapy by p53-dependent indu... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-09-25 |
Journal Detail:
|
Title: The Journal of allergy and clinical immunology Volume: 118 ISSN: 0091-6749 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2006 Nov |
Date Detail:
|
Created Date: 2006-11-07 Completed Date: 2006-12-15 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 1090-6 Citation Subset: AIM; IM |
Affiliation:
|
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Asthma / drug therapy*, metabolism*, physiopathology CD4-Positive T-Lymphocytes / drug effects, metabolism Cells, Cultured Cofilin 1 / biosynthesis*, genetics* Cytokines / antagonists & inhibitors, metabolism, secretion Dexamethasone / antagonists & inhibitors, pharmacology* Female Forced Expiratory Volume / drug effects Glucocorticoids / pharmacology* Humans Immunosuppressive Agents / antagonists & inhibitors, pharmacology Jurkat Cells Male Middle Aged Severity of Illness Index* |
| Chemical | |
Reg. No./Substance:
|
0/Cofilin 1; 0/Cytokines; 0/Glucocorticoids; 0/Immunosuppressive Agents; 50-02-2/Dexamethasone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reversal of airway inflammation and remodeling in asthma by a bispecific antibody fragment linking C...
Next Document: Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma.